Project Summary/Abstract Defects in cell cycle regulation or morphogenetic movements are associated with many pathogenic processes and are regarded as hallmarks of cancer metastasis. Motile cells are often guided non-autonomously by attractive and/or repulsive cues. While many of the cues that guide the various cell migration events that occur during animal development have been identified the downstream molecular mechanisms that integrate these cues into directed motility are poorly understood. Here, I propose to fill this knowledge gap in a comparative context, comparing mesodermal migratory precursors in two distantly related taxa, the roundworm nematode, C. elegans and the zebrafish, D. rerio, using high-resolution sub-cellular microscopy, genetic and genomic approaches. This proposed research will identify how upstream guidance cues regulate cytoskeletal rearrangements and cell cycle state to ensure proper cell migration. Previous data have shown that guidance cues are required for proper cell migration. The specific aims of this proposal seek to (1) determine the role of guidance cues on cytoskeletal organization and dynamics during cell migration and (2) identify how cell cycle regulation controls cell migration. This work will uncover mechanistic information identifying new targets to inhibit cell migration and therapeutically targeting cell migration is a key step in preventing cancer metastasis.